Systemic sclerosis (SSc) is a multifactorial connective tissue disease characterized by autoimmunity, vasculopathy, and progressive fibrosis affecting multiple organs. The fibrotic process, particularly in the skin, lungs, and gastrointestinal tract, is a major cause of morbidity and mortality. Despite extensive research, no effective therapy has been developed to reverse or slow fibrosis. This review highlights recent studies that have elucidated the cellular and molecular mechanisms underlying SSc fibrosis and identified potential therapeutic targets. Key factors include the activation of fibroblasts and myofibroblasts, the role of growth factors and cytokines, and the involvement of specific signaling pathways such as TGF-β and SMAD signaling. Understanding these mechanisms is crucial for developing more effective treatments for SSc.Systemic sclerosis (SSc) is a multifactorial connective tissue disease characterized by autoimmunity, vasculopathy, and progressive fibrosis affecting multiple organs. The fibrotic process, particularly in the skin, lungs, and gastrointestinal tract, is a major cause of morbidity and mortality. Despite extensive research, no effective therapy has been developed to reverse or slow fibrosis. This review highlights recent studies that have elucidated the cellular and molecular mechanisms underlying SSc fibrosis and identified potential therapeutic targets. Key factors include the activation of fibroblasts and myofibroblasts, the role of growth factors and cytokines, and the involvement of specific signaling pathways such as TGF-β and SMAD signaling. Understanding these mechanisms is crucial for developing more effective treatments for SSc.